The only OS most suitable to boot from on a usb model surprisingly seems to offer less usb support namely Linux. The option seen in the bios here with an external usb drive is to see that or one of the two sata drives set as the default boot device.
Once unplugged the entire Windows/software configuration would have to be redone all over. There are external eSata models that simply use an extension cable to an external sata port that runs directly to the board just like an internal sata drive would except the breaks and longer data cable involved.
The usb only as Makaveli213 pointed out already is nothing like a flash drive and best for external storage only. Most external drives see a Fat32 partition and software for Windows and Mac capability. You will most likely want to see that changed to NTFS after downloading the replacement software from the support site.